Studies are initiated to determine the organ and subcellular distribution and metabolism-dependent in vivo and in vitro macromolecular binding of dioxane, the effect of microsomal enzyme inducers and repressors on this binding as well as on dioxane metabolism. In another phase of this study, the structure of the activated, reactive carcinogenic form of dioxane will be elucidated. Again, in another phase the effect of dioxane under chronic, carcinogenic conditions on DNA, RNA and protein synthesis in the target tissues will be studied. An exploration of the structure versus carcinogenic activity relationship of analogs and derivatives of dioxane, and the effect of inducers and repressors of microsomal metabolism on the carcinogenicity of dioxane will be carried out.